Study of the influence of Aspergillus oryzae strain morphology on alternative protein production in bioreactor culture

Abstract

With increasing demands for foods that have a lower environmental impact, are healthy, and have no animal origin, precision fermentation is a powerful tool to meet these requirements. Filamentous fungi traditionally used in industry for producing various food ingredients can also be utilized as a chassis for the heterologous production of alternative proteins. When strains are developed in the laboratory, it is difficult to transpose the technology to bioreactors to scale production. One of the main challenges is controlling the fungus's morphology, which ranges from dispersed to pelleted and interferes with the secretion of the target protein, as well as in the adjustment of bioreactor parameters. No model can predict the best morphology for producing the desired protein. Several physical, chemical, and nutritional factors can interfere with the morphology adopted by the fungus. In this work, we aim to optimize the heterologous production of the alternative proteins ovalbumin, bovine albumin, and growth factor IGF-1 by Aspergillus oryzae, study factors that can modulate the morphology adopted by the fungus in a bioreactor, and determine the optimal morphology for the production of the target protein. We will also describe the behavior of the morphologies adopted by the fungus throughout the process, sequencing (transcriptome), and describe the metabolic pathways and biological processes related to different morphological profiles, secretion of proteins, and adoption of morphologies.